INFUSION OF MODAFINIL INTO ANTERIOR HYPOTHALAMUS OR PEDUNCULOPONTINE TEGMENTAL NUCLEUS AT DIFFERENT TIME-POINTS ENHANCES WAKING AND BLOCKS THE EXPRESS

Clinical studies have indicated that the primary pharmacological activity of modafinil (MOD) is inducing wakefulness; however, the brain targets that underlie its wake-promoting activity have not been described. In the present study, we show that MOD injected into sleep-wake related brain areas promoted alertness. If administered (10, 20, or 30 mu g/1 mu L) into either anterior hypothalamus (AH) or pedunculopontine tegmental nucleus (PFTg) at 08:00, 12:00 or 16:00 h, MOD enhanced wakefulness whereas diminished slow wave sleep as well as rapid eye movement sleep. In addition, microinjection of MOD (10, 20, or 30 mu g/1 mu L.) either into AH or PPTg after total sleep deprivation prevented the sleep rebound. Taken together, these observations suggest that AH and PPTg play a key role in the wake-inducing effects of MOD and encourage further experimentation to draw a possible mechanism of action. (C) 2011 Elsevier Inc. All rights reserved.